Genetic Variant SYT7:p.Arg238Gln (chr11-61542439-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001365809.2(SYT7):c.713G>A(p.Arg238Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,532,704 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0069 ( 6 hom., cov: 33)

Exomes 𝑓: 0.012 ( 120 hom. )

Consequence

SYT7
NM_001365809.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.25

Publications

2 publications found

Variant links:

Genes affected

SYT7 (HGNC:11514): (synaptotagmin 7) This gene is a member of the synaptotagmin gene family and encodes a protein similar to other family members that mediate calcium-dependent regulation of membrane trafficking in synaptic transmission. A similar protein in rodents mediates hormone secretion and lysosome exocytosis. In humans, expression of this gene has been associated with prostate cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2011]

SYT7 links:

ENSG00000256443 (HGNC:):

ENSG00000256443 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0058818758).

BP6

Variant 11-61542439-C-T is Benign according to our data. Variant chr11-61542439-C-T is described in ClinVar as Benign. ClinVar VariationId is 2641831.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365809.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYT7	NM_001365809.2	MANE Select	c.713G>A	p.Arg238Gln	missense	Exon 6 of 13	NP_001352738.1	O43581-3
SYT7	NM_001370210.1		c.275G>A	p.Arg92Gln	missense	Exon 1 of 6	NP_001357139.1
SYT7	NM_001411007.1		c.572+3592G>A		intron	N/A	NP_001397936.1	O43581-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYT7	ENST00000539008.6	TSL:5 MANE Select	c.713G>A	p.Arg238Gln	missense	Exon 6 of 13	ENSP00000439694.1	O43581-3
SYT7	ENST00000540677.5	TSL:1	c.440+3592G>A		intron	N/A	ENSP00000444201.1	O43581-2
SYT7	ENST00000263846.8	TSL:1	c.215+8945G>A		intron	N/A	ENSP00000263846.4	O43581-1

Frequencies

GnomAD3 genomes

AF:

0.00693

AC:

1054

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00246

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00678

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0121

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00557

AC:

727

AN:

130558

AF XY:

0.00568

show subpopulations

Gnomad AFR exome

AF:

0.00163

Gnomad AMR exome

AF:

0.00169

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00690

Gnomad NFE exome

AF:

0.0117

Gnomad OTH exome

AF:

0.00322

GnomAD4 exome

AF:

0.0118

AC:

16247

AN:

1380460

Hom.:

120

Cov.:

AF XY:

0.0113

AC XY:

7694

AN XY:

681122

show subpopulations

African (AFR)

AF:

0.00178

AC:

AN:

31438

American (AMR)

AF:

0.00177

AC:

AN:

35618

Ashkenazi Jewish (ASJ)

AF:

0.0000398

AC:

AN:

25100

East Asian (EAS)

AF:

0.00

AC:

AN:

35688

South Asian (SAS)

AF:

0.00194

AC:

153

AN:

79034

European-Finnish (FIN)

AF:

0.00759

AC:

255

AN:

33614

Middle Eastern (MID)

AF:

0.00235

AC:

AN:

4254

European-Non Finnish (NFE)

AF:

0.0141

AC:

15182

AN:

1078040

Other (OTH)

AF:

0.00914

AC:

527

AN:

57674

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

978

1956

2933

3911

4889

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

588

1176

1764

2352

2940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00692

AC:

1054

AN:

152244

Hom.:

Cov.:

AF XY:

0.00634

AC XY:

472

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.00245

AC:

102

AN:

41548

American (AMR)

AF:

0.00248

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00228

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00678

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0121

AC:

820

AN:

67990

Other (OTH)

AF:

0.00236

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

115

173

230

288

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00337

Hom.:

Bravo

AF:

0.00642

TwinsUK

AF:

0.0162

AC:

ALSPAC

AF:

0.0143

AC:

ExAC

AF:

0.00312

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.60

CADD

Uncertain

(source)

DANN

Uncertain

1.0

Eigen

Benign

0.062

Eigen_PC

Benign

0.084

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0059

MetaSVM

Benign

-0.98

PhyloP100

1.3

PROVEAN

Benign

-0.26

REVEL

Benign

0.047

Sift

Benign

0.036

Sift4G

Benign

0.26

Vest4

0.12

MVP

0.27

ClinPred

0.019

GERP RS

2.9

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over